Primary attention is being devoted to further investigating the phenomenon of major histocompatibility complex (MHC) restriction as it applies to transplantation immunity and immunological tolerance. Thus, employing a variety of inbred and congenic strains of mice and rats, experiments will be undertaken to verify and extend the observation that when tolerance is induced with MHC incompatible bone marrow cells, because these cells migrate to the thymus, their T-cell repertoire is restricted by the Host's MHC. Attempts will also be made to locate the region of the MHC responsible for this restriction phenomenon. Investigations are also planned to further explore the genetic determination of tissue (skin, islets and parathyroid) specific antigens in rats as preliminary observations indicate that these antigens too are MHC restricted, i.e., they only are recognized in association with the MHC of the cell that presents them to the immune system. In this regard, special attention will be devoted to determining the ability of MHC compatible and incompatible islets of Langerhans allografts to cure the diabetes of BB rats, a strain that spontaneously develops a hyperglycemia of autoimmune etiology. Finally, experiments are also planned to determine whether Ia-positive keratinocytes can present antigen, as well as to evaluate the occurrence and persistence of Langerhans cells in the skin of rats. All of these studies bear on a possible solution to the allograft problem, especially with respect to a possible cure for juvenile onset diabetes.